A large number (>12) of human monoclonal antibodies ( HuMoAb) already produced by this laboratory, some known to have highly specific reactivity with myelomonocytic human leukemia cell lines and others with human leukemia cell lines and/or normal hematopoietic cells will be more completely characterized by testing for reactivity against a large panel of human leukemia cell lines, normal hematopoietic cells and leukemic cells from numerous patients. The HuMoAb will also be evaluated by determining the molecular weight of the antigens and/or their composition and that of the epitopes detected by the antibodies, coexpression of the antigens on leukemic cells, effects of antibody on cell growth and differentiation, and the effects of differentiation and activation on antigen expression. Antigens detected by HuMoAb will also be compared with known murine monoclonal antibody defined antigens. These studies will be performed to determine the biological significance of the antigens and the potential biologic significance of the antibodies produced. The ability of the antibodies to mediate complement lysis and antibody dependent cellular cytotoxicity will be studied. Studies will be performed to evaluate the effects of these antibodies on bone marrow stem cells and as therapeutic tools for the elimination of clonogenic leukemia cells from bone marrow samples. Immunotherapy in nude mouse models will be performed. Murine and human anti-idiotypes will be produced and studied in the latter portions of this proposal. Using methods and principles of antibody generation and regulation developed in this laboratory, additional HuMoAb will be produced to selected leukemias and evaluated. Study of these antigens and antibodies will be important in understanding the pathogenesis of these diseases, the role of the host immune response in disease progression, and in the development of potentially therapeutic reagents.